Antibodies directed against idiotypic determinants on anti-staphylococcal nuclease antibodies from different mouse strains have been produced in rats and can be detected by the inhibition of antibody-mediated inactivation of nuclease. These anti-idiotypes have been shown to be specific for the combining site (variable regions) of anti-nuclease antibodies since extensive absorption with normal mouse immunoglobulins fails to diminish their activity, and since antibodies to other sites on the Ig molecule do not inhibit inactivation. As nuclease is an antigen, the response to which is under control of H-2 linked immune response genes, it was of interest to determine the relationship between the idiotype and other genetic loci. By screening a variety of strains and offspring from appropriate matings between strains for the presence of idiotypes and other markers it has been shown that idiotype expression is linked to the heavy chain allotype marker and not to the immune response gene locus. The relationship of the idiotype to the problem of T-cell recognition of antigen is being investigated. BIBLIOGRAPHIC REFERENCES: Berzofsky, J.A., Schechter, A.N., Shearer, G.M., and Sachs, D.H.: Genetic control of the immune response to staphylococcal nuclease. III. Time course and correlation between the immune response to native nuclease and the response to its polypeptide fragments. J. Exp. Med. 145: 111-122, 1977. Berzofsky, J.A., Schechter, A.N., Shearer, G.M., and Sachs, D.H.: Genetic control of the immune response to staphylococcal nuclease. IV. H-2 linked control of the relative proportions of antibodies produced to different determinants of native nuclease. J. Exp. Med. 145: 123-135, 1977.